Synthesis and Stereoisomerism

1)      Stereoisomerism

Isomers

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                        Structural                      Stereoisomers

Isomers                                    ______ï_______

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                                                E/Z isomers       Optical isomers

• Stereoisomers have the same structural formulae but different 3-dimensional arrangements
• There are two types of stereoisomerism: E/Z isomerism, which occurs in alkenes, and optical isomerism, which occurs when a carbon atom is attached to four different groups

2)      E/Z isomers

• E/Z isomers occur in alkenes because of restricted rotation about a double bond
• For E/Z isomers to occur, the two groups at each of the double bond must be different e.g. but-2-ene has E and Z isomers because there is a CH₃- and an H- at each end of the double bond.

                    

Z-but-2-ene                               E-but-2-ene

3)      Optical isomers

• An optical isomer is one that cannot be superimposed on its mirror image
• This occurs when a carbon is attached to four different groups. Such a carbon is known as a chiral centre
• Optical refers to the ability of these molecules to rotate plane-polarised light. D isomers rotate light to the right and L isomers rotate light to the left.
• Most amino acids display optical isomerism e.g. glutamic acid

The central carbon is a chiral centre because it is attached to four different groups:

 -NH₂, -H, -COOH and –CH₂CH₂COOH

1)      General

• A synthesis is a series of reactions giving a desired chemical product
• Answering questions on synthesis requires a good knowledge of the reactions in the current module and the relevant parts of Module F322 (first year)

2)      Synthesis of pharmaceuticals

• Compounds produced naturally in living systems will often be present as one optical isomer only e.g. our bodies only contain L-amino acids
• The synthesis of pharmaceuticals often requires the production of chiral drugs containing a single optical isomer
• Molecules synthesised in a laboratory often contain a mixture of optical isomers whereas molecules of the same compound produced naturally by enzymes in living systems will often be present as only one optical isomer
• Synthesis of a single optical isomer of a pharmaceutical increases costs due to the difficulty in separating the optical isomers but has the benefits of reducing side effects and improving pharmacological activity
• Modern synthesis of a single optical isomer of a pharmaceutical is often carried out:
• Using enzymes or bacteria which promote stereoselectivity
• Using chemical chiral synthesis or chiral catalysts
• Using natural chiral molecules, such as L-amino acids or sugars, as starting materials